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Reliable assessment of protection in venom immunotherapy (VIT) patients remains a clinical challenge, especially due to the limitations of conventional sting challenge tests (SCTs), which require complex insect handling and may compromise test accuracy. This study introduces StingReady, a novel, user-friendly device designed to streamline the SCT process by enabling safe, efficient, and minimally manipulative exposure to hymenopteran stings. For the first time, StingReady was applied to conduct SCTs with Vespa velutina, an invasive hornet species of increasing clinical relevance. The device was tested in a real-world setting at Belvís Park in Santiago de Compostela, Spain, where hornets were successfully captured and transported to the hospital without anesthesia or limb removal. The design features adjustable mesh sizes, allowing compatibility with various hymenopteran taxa. Using StingReady, nine patients underwent SCTs with no need for direct insect handling during the hospital procedure. The process improved patient safety and comfort while preserving the insect’s natural stinging behavior, thereby enhancing test reliability. This study demonstrates that StingReady significantly improves SCT methodology, offering a practical, reproducible, and ethically sound alternative for evaluating VIT efficacy across diverse hymenopteran species.

Background Efficacy of allergen immunotherapy is dose‐dependent; however, high doses of allergen may imply a greater risk of adverse reactions. Objective To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites. Methods An open‐label, noncontrolled, nonrandomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build‐up phase on the first day (0.2 mL and 0.3 mL with a 30‐min interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months. Results Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥ 2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty‐nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects. Conclusions SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile. It is an open‐label, noncontrolled, nonrandomised, phase IIb clinical trial. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL). The treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld at maximum concentrations showed a favourable safety profile.

Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients’ asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

This multicentre, cross-sectional study conducted in Spain assessed the clinical characteristics and quality of life of patients who were aged 14–55 years and had allergic rhinitis and/or asthma, which was due to house dust mite sensitisation, for at least 2 years. Overall, 296 patients were included; 60% had allergic rhinitis (mostly persistent moderate-to-severe) and 40% had rhinitis and asthma (mostly intermittent or mild-to-persistent). Patients with rhinitis had moderately reduced quality of life, which was significantly worse in adults than adolescents. The impact of asthma on quality of life was less pronounced than that of rhinitis. Our findings show that allergic asthma and/or rhinitis due to house dust mites have a moderately negative impact on quality of life, particularly in adults, and that quality of life is significantly influenced by rhinitis.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome’s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153 , OPG204 , and OPG208 , could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability. The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.

Background Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. Methods A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. Results In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration ( P value for false discovery rate ( P FDR ) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies ( P FDR  < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression ( P  = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. Conclusions The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.

Cosaviruses (CoSV) and Saffold cardiovirus (SAFV) are novel members of the Picornaviridae family. The Matanza-Riachuelo river basin covers a total area of 2200 km2 with approximately 60 km long. Its last section is called Riachuelo River. The aim of this study was to describe the circulation of both picornaviruses and their relationship with the environmental situation of the Riachuelo River using 274 samples collected from 2005 to 2015. CoSV and SAFV were investigated in samples available by two periods: 2005–2006 and 2014–2015 (103 and 101, respectively). Physicochemical and bacteriological parameters confirmed very high levels of human fecal contamination during the 11 years evaluated. CoSV was detected in 85.7% (66/77) and 65.4% (17/26) of the samples collected in 2005–2006 and 2014–2015 periods, respectively. Species A and D were identified, the first one being widely predominant: 74.1% (20/27) and 75.0% (3/4) in both periods. SAFV virus was detected in 47.1% (32/68) and 52.6% (10/19) in periods 2005–2006 and 2014–2015, respectively. SAFV-6 was the most identified genotype in the entire study, while SAFV-3 was predominant in 2005–2006. The contribution of genotypes 1, 2, 4 and 8 was minor. The high prevalence of CoSV and SAFV suggests that both viruses have been circulating in Argentina at least since 2005. Our results show that a watercourse with high rates of human fecal contamination can become a persistent source of new viruses which capacity to produce human diseases is unknown.

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu’s arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5–50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0–31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5–50.0) to 5.0 (0.0–5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0–14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0–46.0) versus 45.0 (38.0–57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0–38.0) versus 6.0 (1.0–23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7–5.6) versus 1.3 (0.3–3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.